The major histocompatibility complex (MHC) of the mouse codes for a number of 40-50,000 dalton glycoprotein cell surface antigens which are associated with Beta-2-microglobulin (B2M): H-2K, H-2D, H-2L, Qa-2 and TL. We propose to examine several biochemical-genetic features of these antigens. 1) We have recently described genetic polymorphism of B2M, detected by electrophoretic comparison of B2M from different inbred mouse strains. This is the first evidence of B2M allelism to be found in any species. These variants have been named B2M-A (A strain) and B2M-B (B6 strain). (B2M-B runs faster on SDS polyacrylamide gel electrophoresis than B2M-A.) Typing of H-2 congenic mice has shown that the locus for this variation is not closely linked to the MHC. We propose to determine the molecular basis of this allelism by peptide mapping and other biochemical methods as well as produce alloantisera which might recognize B2M. We will also carry out the genetic analysis of this putative marker of the B2M structural gene including test-crosses, strain distribution, linkage tests and construction of B2M congenic strains. 2) We have recently completed studies of the TL alloantigen on thymocytes. It was found that the TL antigenic determinants reside on a single 45K TL molecular species and that the genetic polymorphism of TL is determined by variation of its amino acid composition. We propose to study TL molecules on leukemias, with particular emphasis on the question of the number of TL molecular species and the relation of leukemia-specific TL molecules to thymocyte TL. 3) We have recently detected, by biochemical methods, a new 40,000 dalton molecule which appears to be determined by the MHC. We propose to characterize this molecule biochemically and genetically, including determination of MHC subregion origin, strain distribution, association with B2M, and serological analysis. Taken together, these studies should add to our knowledge of the MHC antigens, which are of central importance in transplantation biology, immunogenetics and immunobiology.